Introduction to Immunology (text pages: 727-760) • What happens if some bacterium manages to get through the passive defense

mechanisms like skin and mucous membranes? • What mechanisms exist to fight a potential infection

o Non-specific immunity o Specific immunity

Non-specific active immunity

• A resistance to infection mediated by white blood cells • Derived from bone marrow stem cell and differentiate into

o Myeloid precursors which give rise to Mast cells Polymorphonuclear leukocytes Monocytes

• Which in turn differentiate into macrophages • And into Dendritic cells

o Lymphoid precursors which give rise to T cells (thymus processed) B cells (bone marrow processed

• Which in turn give rise to • Plasma cells • Memory cells

Some of these cells have the ability to phagocytize foreign material

• PMNs o granular appearance due

to the presence of materials that will attack foreign material

o found in blood, but can move out of blood stream into extra-vascular areas (diapedisis)

• Monocytes o Circulating o Capable of diapedisis o Differentiate into

monocyte and dendritic cells

o All types are found in lymph nodes and spleen

Action of phagocytosis • Attachment

o Receptors on phagocyte surface recognize molecular patterns on bacteria or viruses. For example a receptor may recognize the molecular pattern of LPS and initiate a phagocytosis sequence

• Ingestion • Phagosome formation • Phagolysosome formation • Lysis

This mechanism is not always effective. Some organisms may live within the phagolysosome. Recall ‘leucocidins’. Mechanisms of diapedisis improved by events associated with infection or injury

• Damaged connective tissue cells, mast cells, release agents (cytokines) that promote diapedisis

o Histamine Effective vasodilator, increases vascular permeability

o Kinins a class of substances with multiple effects

• Actions is to draw phagocytes to the area of injury or infections • Activate the phagocytes to engulf pretty much everything around.

• Pus…a large accumulation of PMNs and monocytes Specific Active Immunity

• Phagocytes are the first cells involved with developing some type of immunity. While their role seems non-specific in that, any foreign material may be attacked. During degradation of the foreign material, the antigen, is processed, bound to protein known as the Major Histocompatibility Complex (MHC) and passed through the cytoplasmic membrane to the surface of the cell.

MHC

• Proteins present in all vertebrates • The proteins that allow cells to identify self from non-self • They act as a template containing the information that the phagocyte captures • Two types

o Class I are found on the surfaces of all nucleated cells o Class II are found on the surface of B cells, macrophages, and dentritic

cells So what happens • For foreign material phagocytized,

• Some material is combined with the MHC (Type II proteins) in the phagolysosome and moved to the cell surface

• For a foreign material originating within cells (viruses or tumor material)

• Proteins processed by the cell itself (the infected cell), imbedded in the MHC (Type I proteins) and moved to the cell surface

Other cells of the immune system have on their surfaces receptors

• T-Cells o T-Cell Receptors

Membrane spanning proteins that extends to the cell surface Each T-cell has thousands of copies of the same receptor T-cells are different from each other

o the MHC serves as a reference

point for the T-cell receptor which recognizes the antigen imbedded within

What happens upon recognition?

• Depends on the type of T cell and the type of antigen

• Cytotoxic T Cells o T cells known as T-cytotoxic cells,

produce toxic proteins that kill the cell containing the antigen

o Active with Class I type antigens • Natural Killer Cells

o A form of cytotoxic T cells that target cells types lacking MHC

• Helper T Cells: Type I o Secrete agents (cytokines) that stimulate activity of macrophages

• Helper T Cells: Type II o B Cells bind antigens to proteins on their surface and internally process

the foreign material. o Antigens are presented on the MHC complex o TH2 cells interact with the MHC-antigen complex and release cytokines

that stimulate the B-cell to Proliferate as Plasma Cells Produce memory cells

• Plasma cells o Produce antibodies with react specifically

with the antigen o Short lived

• Memory cells o Upon repeated exposure to the antigen these will clone as plasma cells and

produce antibodies

A general summary of events

So…What are antibodies and what role to they play? • Antibodies or immunoglobulins (Ig) are proteins that are able to combine with

antigens. • Found in serum and other

body fluids • Proteins have a distinctive

structure o Variable fragments o Fixed Fragments

Variable classes of immunoglobins

So what happens during a response to an antigen?

• Processing of the antigen by white blood cells

• If processed by B-cells o Plasma cells and memory cells are

produced o Initially IgM is active against the

antigen but eventually IgG is produced

o Review Primary Response and Seconday Response

• Antibodies react with antigens in a variety of ways

o Causing cell lysis o Neutralizing toxins o Opsonizing agents (promote phagocytosis) o Precipitation soluble antigens o Agglutination of cells

Review blood typing and RhoGam

How do vaccinations work? • Review types of antigens

o Toxoids o Cellular o Attenuated

• Why do we vaccinate at certain times?

Types of Immunity

• Naturally Acquired o Active: You get the disease o Passive: in vivo protection (cross placental IgG, colostrums IgA)

• Artificially Acquired o Active: Vaccination o Passive: administration of blocking antibody

So what’s deal with allergies?

• Allergies are known as hypersensitivities • Multi-step events requiring exposure to an antigen followed by a dormant stage

when you become sensitized • Second exposure is not good.

Immediate type hypersensitivity • Review events

o Involvement of mast cells Connective tissue cells particularly numerous in respiratory and

gastrointestinal tracts near blood vessels Upon degranulation skin become swollen, eyes bulge, general hives,

joints swell, cramps Very Nasty.

• Event known as Anaphylactic shock o Compare systemic to localized reactions

• Treatment o Usually adrenalin for systemic o Mediators for localized reactions (antihistamine)

• Typical agents o Bee venom o Some proteins o Some drugs

• Review desensitization by blocking antibody

Delayed type hypersensitivity • Mediated by TH1 cells • Prior exposure sensitizes T cells • Second exposure T cells secrete cytokine which

o Draws phagocytes to the area o Causes localized swelling and redness o Itchyness

• Commonly known as contact dermatitis • Examples

o Tuberculin tine test o Poison ivy reactions o Animal dander reactions

Autoimmune types • Usually involve antibody production against “self” tissues • Result is never good • Examples include

o Myasthenia gravis (against muscle) o Goodpasture’s syndrome (against kidney) o Lupus erythematosis (DNA, blood clotting proteins o Rheumatoid arthritis (cartilage)

All figures except where noted, are from Madigan et al. 2002 or Madigan et al. 2000 References: Madigan, M. T., J.M. Martinko, and J. Parker. 2002. Brock Biology of Microorganisms 10th ed. Prentice Hall. Madigan, M. T., J.M. Martinko, and J. Parker. 2000. Brock Biology of Microorganisms 9th ed. Prentice Hall.